title: Molecular basis of hippocampal energy metabolism in diabetic rats: the effects of SOD mimic.
abstract: Hippocampal structural changes associated with diabetes-related cognitive impairments are well described, but their molecular background remained vague. We examined whether/how diabetes alters molecular basis of energy metabolism in hippocampus readily after diabetes onset, with special emphasis on its redox-sensitivity. To induce diabetes, adult Mill Hill hybrid hooded rats received a single alloxan dose (120 mg/kg). Both non-diabetic and diabetic groups were further divided in two subgroups receiving (i) or not (ii) superoxide dismutase (SOD) mimic, [Mn(II)(pyane)Cl2] for 7 days, i.p. Treatment of the diabetic animals started after blood glucose level ≥12 mM. Diabetes decreased protein levels of oxidative phosphorylation components: complex III and ATP synthase. In contrast, protein amounts of glyceraldehyde-3-phosphate dehydrogenase, pyruvate dehydrogenase, and hypoxia-inducible factor-1α - the key regulator of energy metabolism in stress conditions, were higher in diabetic animals. Treatment with SOD mimic restored/increased the levels of oxidative phosphorylation components and returned hypoxia-inducible factor-1α to control level, while diabetes-induced up-regulation of glycolytic enzyme, glyceraldehyde-3-phosphate dehydrogenase, was additionally stimulated. To conclude, our results provide insight into the earliest molecular changes of energy-producing pathways in diabetes that may account for structural/functional disturbance of hippocampus, seen during disease progression. Also, data suggest [Mn(II)(pyane)Cl2] as potential therapeutic agent in cutting-edge approaches to threat this widespread metabolic disorder.
authors.affiliation: University of Belgrade, Institute for Biological Research "Siniša Stanković", Department of Physiology, Belgrade, Serbia.
authors.forename: Ana
authors.initials: A
authors.lastname: Stančić
authors.forename: Vesna
authors.initials: V
authors.lastname: Otašević
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Janković
authors.forename: Milica
authors.initials: M
authors.lastname: Vučetić
authors.forename: Ivana
authors.initials: I
authors.lastname: Ivanović-Burmazović
authors.forename: Miloš R
authors.initials: MR
authors.lastname: Filipović
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Korać
authors.forename: Milica
authors.initials: M
authors.lastname: Markelić
authors.forename: Ksenija
authors.initials: K
authors.lastname: Veličković
authors.forename: Igor
authors.initials: I
authors.lastname: Golić
authors.forename: Biljana
authors.initials: B
authors.lastname: Buzadžić
authors.forename: Bato
authors.initials: B
authors.lastname: Korać
mesh_terms: D000496:Alloxan; D000818:Animals; D006152:Cyclic GMP / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000473:pathology*; D004195:Disease Models, Animal; D014450:Electron Transport Complex III / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006624:Hippocampus / Q000503:physiopathology*; D051793:Hypoxia-Inducible Factor 1 / Q000378:metabolism; D007658:Ketone Oxidoreductases / Q000378:metabolism; D008297:Male; D025261:Mitochondrial Proton-Translocating ATPases / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D051381:Rats; D013389:Succinate-CoA Ligases / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism*
chemical_list: D051793:Hypoxia-Inducible Factor 1; D000496:Alloxan; D045304:Cytochromes c; D052248:Nitric Oxide Synthase Type I; D013482:Superoxide Dismutase; D007658:Ketone Oxidoreductases; C053164:pyruvate dehydrogenase (NADP+); D025261:Mitochondrial Proton-Translocating ATPases; D013389:Succinate-CoA Ligases; D014450:Electron Transport Complex III; D006152:Cyclic GMP
keywords: Diabetes; Glycolysis; Hippocampus; Oxidative phosphorylation; SOD mimic